Trypanosoma cruzi downregulates the production of interleukin-2, interferon-gamma, interleukin-4 and interleukin-5 by activated human lymphocytes.

The intracellular levels of interleukin (IL)-2, IL-4, IL-5 and interferon-gamma (IFN-gamma) produced by mitogen-stimulated normal human blood lymphocytes were found to be markedly reduced in cultures containing purified Trypanosoma cruzi trypomastigotes. This was evidenced by marked decreases in the proportion of lymphocytes whose cytoplasm was stained with fluorochrome-conjugated monoclonal antibodies specific for the selected cytokines and a somewhat small but systematically demonstrable reduction in the mean fluorescence intensity of the stained lymphocytes relative to values obtained with parasite-free cultures. The percentage of activated CD3+ cells containing both IL-2, IL-4, i.e., THO-like cells, was also much smaller in the cultures containing trypomastigotes, indicating that T. cruzi can concomitantly inhibit the production of more than 1 cytokine by individual activated T lymphocytes. These results evidence the ability of T. cruzi to down-regulate the production of several important cytokines and raise the possibility of a direct role for this parasite in altering cytokine production during infection.